This invention relates to a prophylactic, therapeutic agent capable of inhibiting bone loss which is found in osteoporosis.
In Japan, the population of aged persons is sharply increasing, and various social problems occur therewith. One of the problems is in nursing of the aged persons. Most of the aged persons who require nursing are bedridden, except for persons suffering from cranial nerve troubles, such as dementia. The greatest cause which makes aged persons bedridden is bone fracture caused by osteoporosis. Therefore, it is very important to prevent osteoporosis.
Osteoporosis is caused by trouble in the relationship between resorption and formation of the bone, and various reasons are pointed out, such as metabolic troubles and internal secretion troubles. Various medicines have already been developed.
Estrogen is a female hormone which inhibits resorption of the bone. It has already been used in clinical fields for the medical treatment of osteoporosis and its medical effects have been confirmed. However, its relevance to uterine cancer has been pointed out, and therefore, it cannot be said that it has no problems.
Thereupon, phytoestrogen is being investigated as an alternative. Phytoestrogen is contained in plant, and exhibits female hormone-like action. As representative components thereof, genistein and daidzein are known, which are isoflavons of soybean, and enterolactone and enterodiol are further known, which are lignars contained in rye, blueberry, sesame, tea and so on.
As a result, it has become apparent that phytoestrogen also has the action of inhibiting bone loss, and investigations are advanced for putting it to practical use (Biol. Pharm. Ball., 21(1) 62-66 (1998), J. Nutr. 126: 161-167, 1996, J. Nutr. 126: 176-182, 1996). However, its effects are still insufficient.
An object of the invention is to provide an agent which prevents the reduction of bone density occurring with the outbreak and progress of osteoporosis and exhibits excellent effects for the prevention and medical treatment of osteoporosis.
The inventors investigated eagerly in order to achieve the above object, and as a result, they found that the reduction of bone density can be improved remarkably by combining an indigestible oligosaccharide, such as fructooligosaccharides, with phytoestrogen.
The present invention has been made based on this finding, and relates to a prophylactic, therapeutic agent for osteoporosis which comprises phytoestrogen and an ingestible oligosaccharide.
Although the function and mechanism are not entirely clear, it can be assumed that enteric bacteria, such as Bifidobacterium bifidum having a high xcex2-glucosidase activity, are increased by the intake of the indigestible oligosaccharide, and absorption of phytoestrogen is raised thereby steadily. That is, natural phytoestrogen is combined with a sugar chain to form a glycoside, and its absorption by an organism is not possible until the sugar chain is cut off. The cutting off of the sugar chain is made mainly by bacteria existing in the large intestine. However, the type and quantity of the bacteria greatly differ between individuals, and in some persons, the absorption hardly occurs. It can be considered that enteric bacteria are increased or their activities are raised by the combination of the indigestible oligosaccharide, and the sugar chain is cut off phytoestrogen at a high rate to raise the absorption rate of phytoestrogen.
Phytoestrogen is contained in plant, and exhibits female hormone-like action. The phytoestrogen is a substance called SERM (Selective estrogen receptor modulator) contained in plants, and exhibits a similar action to female hormones in an organ specificity viewpoint, such as interacting with a receptor of estrogen which is a female hormone and inhibiting resorption of the bone. The phytoestrogen is an isoflavon, such as genistein or daidzein, which are isoflavons of soybean, a lignan, such as enterolactone or enterodiol, or the like. Plants containing phytoestrogen in quantity are soybean, rye, blueberry, sesame, tea and so on. The phytoestrogen applicable to the prophylactic, therapeutic agent for osteoporosis of the invention may be in a form of the above food itself or a fabricated one thereof as well as an extracted semipurified one.
The indigestible oligosaccharide is a disaccharide to pentacontasaccharide, preferably a disaccharide to pentasaccharide, which is not digested by the digestive enzymes in an organism, and preferred ones increase absorption of calcium in the intestines. Preferable examples are fructooligosaccharides, raffinose, galactooligosaccharides, xylooligosaccharides and the like. The fructooligosaccharides are a designation of a mixture of sugars having a similar structure to sucrose which are formed by bonding 1 to 3 fructose molecules to the fructose residue of sucrose. Each sugar is named 1-kestose (GF2), nystose (GF3) and fructo-furanosyl nystose (GF4) from the shortened chain length one. The galactooligosaccharide is a generic term for 2 to 6 sugar oligosaccharides formed by reacting xcex2-galactosidase with lactose (disaccharide composed of galactose and glucose bonded by a xcex2-1,4-bond). A representative component of the galactooligosaccharide is 4xe2x80x2-galactosyl lactose (hereinafter abbreviated as 4xe2x80x2-GL) having a structure composed of lactose and galactose bonded through a xcex2-1,4-bond. As the other components, there are tetra to hexasaccharides formed by further bonding galactose molecule(s) to 4xe2x80x2-GL through xcex2-1,4-bond(s), disaccharides composed of galactose and glucose bonded through a xcex2-1,3-bond, and so on. The structure of the galactooligosaccharide is shown below: 
The xylooligosaccharide is a sugar derived from hemicellulose having a structure composed of about 2 to 7 xylose molecules bonded through xcex2-1,4-bond(s). Some xylooligosaccharides have a side chain of arabinose, glucuronic acid, etc. The indigestible oligosaccharide may be a crude product as well as a purified one.
A suitable content ratio of phytoestrogen and the indigestible oligosaccharide is about 1:10 to 1:1,000, preferably about 1:100 to 1:500.
The prophylactic, therapeutic agent of the invention may not contain calcium.
The prophylactic, therapeutic agent of the invention is taken orally, and a suitable unit ingestion is about 1 to 100 mg, preferably about 10 to 50 mg as the weight of phytoestrogen per 1 kg of body weight.